This proposal aims to investigate host and microbial genomic determinants of febrile illness in West Africa and establish the West African GEnomic Research (WAGER) Network, consisting of West African Francophone and Anglophone centers of excellence in Nigeria, Sierra-Leone and Senegal. The partners in these three countries have a long-term track record of successful collaboration with each other and with US partners at the Broad Institute, Harvard University, and Tulane University studying the devastating diseases Lassa fever (LF) and Plasmodium falciparum malaria. Moreover, we have a demonstrated deep investment in capacity building and training of African scientists. We recognize that in order to truly participate in this genomic revolution, African researchers must be equipped not only to enable large-scale genomics projects, but also to carry out fully independent research projects, from beginning to end. Febrile illness in Africa is a devastating burden to the continent, and its study is a place in which both large-scale consortium projects and small field studies can have a major impact. In this proposal we will greatly enhance efforts for training and supporting cutting-edge genomics research on health in Africa. We will carry our annual rigorous trainings at the Broad Institute and at WAGER sites and develop them into a larger training program that can be used by all H3Africa partners. We will create a core genomics center at Redeemer's University with an lllumina MiSeq and lay the groundwork to collect 750 high quality samples from febrile patient per year from each of the three WAGER field sites. With these foundations in place, we will use both field-deployed and state-of-the-art genomic technology to identify pathogens driving febrile illness and to examine the genetic basis of infectious disease susceptibility. We will do this through four projects two of which are focused on field-deployable genomic diagnostics and can be carried out at the local sites. The projects are (1) Identifying Microbes Underlying Fever of Unknown Origin (FUO) Through Field Diagnostics; (2) Characterizing FUO through Microbial Metagenomics; (3) Examining Human Genetic Determinants of LF and Malaria; and (4) Identifying Human Genetic Determinants of LF Through Genome-Wide Association.